Nashville, TN—An allergic reaction to the first mRNA COVID-19 vaccines doesn’t automatically exclude a second dose, according to a new study.

In fact, a multihospital analysis of those who had an allergic reaction to their first shot found that all were able to receive a second dose without complications.

The study points out that allergic reactions after mRNA COVID-19 vaccinations have been reported to be as high as 2%, although anaphylaxis—a life-threatening whole-body allergic reaction—has occurred in only 2.5 per 10,000 people.

The research, reported in JAMA Internal Medicine, sought to determine whether it’s safe to continue with a second mRNA COVID-19 vaccine dose after a first-dose reaction. Data were combined from patients who had that outcome from Massachusetts General Hospital in Boston, Vanderbilt University Medical Center in Nashville, Tennessee, University of Texas Southwestern Medical Center in Dallas, Texas and Yale School of Medicine in New Haven, Connecticut.

“These reactions could include symptoms such as itching or hives or flushing. The patients included were all advised by allergy specialists after their dose one reaction,” explained co-lead author Matthew S. Krantz, MD, of Vanderbilt University Medical Center.

Whether to administer a second dose of mRNA COVID-19 vaccine after a first-dose reaction has been a concern for pharmacists and other vaccinators. In an effort to address those worries, the researchers took a close look at the safety of the second dose of Pfizer-BioNTech or Moderna vaccine in those with a history of immediate and possibly allergic reactions to the first dose.

The retrospective study looked at records from January 1, 2021, to March 31, 2021, including patients with an immediate allergic reaction to the Pfizer-BioNTech or Moderna vaccine.

That was defined as:
• Symptom onset within 4 hours of dose 1
• At least one allergic symptom
• Referral for an allergy/immunology consultation with in-clinic or telehealth assessment

Ultimately, 189 patients, 86% women with a mean age of 43 years, participated in the study. Most of the first-dose reactions evaluated, 69%, were to Moderna and 31% to Pfizer-BioNTech. Most frequently reported were flushing or erythema (53 [28%]), dizziness or lightheadedness (49 [26%]), tingling (46 [24%]), throat tightness (41 [22%]), hives (39 [21%]), and wheezing or shortness of breath (39 [21%]).

Only 32 (17%) met anaphylaxis criteria. Investigators scored anaphylaxis using the Brighton and the National Institute of Allergy and Infectious Diseases/Food Allergy and Anaphylaxis Network criteria and confirmed anaphylaxis required meeting at least one of the two criteria.

Defined as the primary outcome was second-dose tolerance; patients were deemed to have met it if they had no immediate symptoms after second-dose administration or symptoms that were mild, self-limited, and/or resolved with antihistamines alone.

For those patients who did not have their second dose observed by allergy/immunology departments, clinical details were gathered through telephone calls.

Most of the patients, 84%, received a second dose, with 30% of them receiving. antihistamine premedication.

“All 159 patients, including 19 individuals with first-dose anaphylaxis, tolerated the second dose,” the researchers report. “Thirty-two (20%) reported immediate and potentially allergic symptoms that were associated with the second dose that were self-limited, mild, and/or resolved with antihistamines alone.”

The authors note that their study “supports the safety of Pfizer-BioNTech or Moderna vaccine second dose administration in patients who report immediate and potentially allergic reactions after the first dose. Although mild symptoms were reported in 20% of patients with second dose administration, all patients who received a second dose safely completed their vaccination series and could use mRNA COVID-19 vaccines in the future when indicated.”

The researchers posit that, because second-dose tolerance occurred following reactions to the first dose, many of the initial reactions might not have been truly allergic reactions. Instead, they suggest, the symptoms could have been caused by a non–immunoglobulin E–mediated mechanism, adding that, in those cases, symptoms can typically be moderated with premedications.

“One important point from this study is that these immediate onset mRNA vaccine reactions may not be mechanistically caused by classic allergy, called immediate hypersensitivity or Ig-E-mediated hypersensitivity. For classic allergy, re-exposure to the allergen causes the same or even worse symptoms,” explained cosenior author Kimberly G. Blumenthal, MD, MSc, codirector of the Clinical Epidemiology Program within the Massachusetts General Hospital (MGH) Division of Rheumatology, Allergy and Immunology.

The study also notes that, with the emergency-use authorization of the Janssen vaccine, the CDC recommended that individuals with an immediate and potentially allergic reaction to the first dose of the Pfizer-BioNTech or Moderna mRNA COVID-19 vaccine could receive a Janssen single dose subsequently. “However, our data suggest that most patients with immediate and potentially allergic reactions to mRNA COVID-19 vaccines tolerate a second dose. Therefore, it may not be necessary to consider this, to our knowledge, largely unstudied alternative mixed series approach,” the authors add.

The study’s findings suggest that it’s safe for most individuals to receive a second dose of the mRNA COVID-19 vaccine, notes cosenior author Aleena Banerji, MD, clinical director of the Allergy and Clinical Immunology Unit at MGH. “After first dose reactions, allergy specialists may be useful to help guide risk/benefit assessments and assist with completion of safe vaccination.”

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